Current understanding of the structure-function relationship in macromolecules is derived in large part from determination of the three- dimensional structure of these molecules in solution. This project focuses on determination of the conformational structure of synthetic oligonucleotides, and the interaction of these with various drugs. One may obtain inter-proton distances within complex biomolecules, as well as scalar coupling constants using two-dimensional NMR techniques. The coupling constants are indicative of dihedral angles between nuclei, and may be converted to internuclear distances. These distances, along with those obtained from Nuclear Overhauser experiments, are used in conjunction with distance geometry calculations to generate a three- dimensional structure. Complete relaxation matrix analysis of the spins is used to further refine the structure. This yields a family of similar structure in a method analogous to restrained molecular dynamics. For the oligonucleotide (ATATCGTACGATAT)2, the conformation was determined to be of the general B family, with some local perturbations of structure. However, the major difficulty of this procedure is the under-determination of the phosphodiester backbone. Heteronuclear experiments, specifically those involving 31P and 13C, have improved the situation, as the chemical shifts of both nuclei depend on the backbone conformation. Additional torsion angle constraints have also been obtained from the 31P-1H heteronuclear correlation experiment. The x-ray crystal structure of the complex between the anticancer drug daunomycin and the oligonucleotide (CGTAGG)2 showed that the drug intercalated between sequential CG base pairs. In this laboratory, preliminary NMR investigations showed that the DNA/drug complex exchanged slowly on the NMR time scale, while 31P exchange spectra indicated that the site of intercalation was the same as in the crystal. Additional evidence was obtained from the NOESY spectrum, which showed intermolecular crosspeaks between the drug and the DNA. Finally, an estimate of the residence time of the drug at the intercalation site was determined to be approximately 10 ms, based on linewidth considerations.